tbuckley/cabot-search huggingface dataset:
Adverse pregnancy outcomes and long term risk of ischemic heart disease in mothers: national cohort and co-sibling study
Authors: Casey Crump, Jan Sundquist, Mary Ann McLaughlin, Siobhan M Dolan, Usha Govindarajulu, Weiva Sieh, Kristina Sundquist
Journal: BMJ (2023)

Abstract Objective To examine the associations between five major adverse pregnancy outcomes and long term risks of ischemic heart disease in mothers. Design National cohort study. Setting Sweden. Participants All 2 195 266 women with a first singleton delivery in Sweden during 1973-2015. Main outcome measures The main outcome measure was incidence of ischemic heart disease from delivery to 2018, identified from nationwide inpatient and outpatient diagnoses. Cox regression was used to calculate hazard ratios for ischemic heart disease associated with preterm delivery, small for gestational age, pre-eclampsia, other hypertensive disorders of pregnancy, and gestational diabetes, adjusting for other adverse pregnancy outcomes and maternal factors. Co-sibling analyses assessed for confounding by shared familial (genetic and environmental) factors. Results During 53.6 million person years of follow-up, ischemic heart disease was diagnosed in 83 881 (3.8%) women. All five adverse pregnancy outcomes were independently associated with increased risk of ischemic heart disease. In the 10 years after delivery, adjusted hazard ratios for ischemic heart disease associated with specific adverse pregnancy outcomes were 2.09 (95% confidence interval 1.77 to 2.46) for other hypertensive disorders of pregnancy, 1.72 (1.55 to 1.90) for preterm delivery, 1.54 (1.37 to 1.72) for pre-eclampsia, 1.30 (1.09 to 1.56) for gestational diabetes, and 1.10 (1.00 to 1.21) for small for gestational age. The hazard ratios remained significantly increased even 30-46 years after delivery: 1.47 (1.30 to 1.66) for other hypertensive disorders of pregnancy, 1.40 (1.29 to 1.51) for gestational diabetes, 1.32 (1.28 to 1.36) for pre-eclampsia, 1.23 (1.19 to 1.27) for preterm delivery, and 1.16 (1.13 to 1.19) for small for gestational age. These findings were only partially (&lt;45%) explained by shared familial (genetic or environmental) factors. Women who experienced multiple adverse pregnancy outcomes showed further increases in risk (eg, &lt;10 years after delivery, adjusted hazard ratios associated with 1, 2, or ≥3 adverse pregnancy outcomes were 1.29 (1.19 to 1.39), 1.80 (1.59 to 2.03), and 2.26 (1.89 to 2.70), respectively)). Conclusions In this large national cohort, women who experienced any of five major adverse pregnancy outcomes showed an increased risk for ischemic heart disease up to 46 years after delivery. Women with adverse pregnancy outcomes should be considered for early preventive evaluation and long term risk reduction to help prevent the development of ischemic heart disease.
Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): a randomised, double-blind, controlled, phase 2, proof-of-concept trial
Authors: Brian G Feagan, Bruce E Sands, William J Sandborn, Matthew Germinaro, Marion Vetter, Jie Shao, Shihong Sheng, Jewel Johanns, Julián Panés, Alexander Tkachev, Dilara Kalimullina, Robert Petryka, Marina Osipenko, Nataliia Tsarynna, Leonid Bilianskyi, Dariusz Kleczkowski, Andrii Yurkiv, Marek Woynarowski, Orest Abrahamovych, Olha Ivanishyn, Grazyna Rydzewska, Jaroslaw Kierkus, Elina Petrova, Olga Vasilevskaya, Halyna Afanasieva, Carlos Francesconi, Jaroslaw Leszczyszyn, Elena Bunkova, Dmitry Platonov, Olena Datsenko, Oleksii Gridnyev, Ihor Hospodarsky, Liudmyla Prystupa, Mykola Stanislavchuk, Anatoly Pershko, Oksana Shchukina, Vladimir Simanenkov, Oleksandr Golovchenko, William Holderman, Juan Lasa, Jakob Begun, Maria de Lourdes de Abreu Ferrari, Pedro Lopez, Andrey Obrezan, Shiraz Farooq, Felix Tiongco, Abel Novillo, Emiliano Tron, Finlay Macrae, Rupert Leong, Ligia Yukie Sassaki, Cyrla Zaltman, Roberto Kaiser Junior, Andreas Stallmach, Jochen Klaus, Manuel Martinez, Azalia Ruiz, Rustem Abdulkhakov, Vishvinder Sharma, Louis Korman, James Lord, Bhaktasharan Patel, Timothy Ritter
Journal: The Lancet. Gastroenterology & hepatology (2023)
Israel decides to cancel sweetened beverage tax in setback to public health
Authors: Aron M Troen, Ana Paula Bortoletto Martins, Ildefonso Hernandez Aguado, Barry Popkin, Dariush Mozaffarian, Martin Caraher, Amy Lazarus Yaroch, Miguel Ángel Royo Bordonada, Hagai Levine
Journal: The Lancet (2023)
Association of type 2 diabetes according to the number of risk factors within the recommended range with incidence of major depression and clinically relevant depressive symptoms: a prospective analysis
Authors: April C E van Gennip, Miranda T Schram, Sebastian Köhler, Abraham A Kroon, Annemarie Koster, Simone J P M Eussen, Bastiaan E de Galan, Thomas T van Sloten, Coen D A Stehouwer
Journal: The Lancet Healthy Longevity (2023)
A Breathtaking Discovery
Authors: Jonathan Coraor Fried, John J. Ross, Zoe F. Weiss, Bruce D. Levy, Joseph Loscalzo
Journal: New England Journal of Medicine (2023)

A 76-year-old man presented during the summer of 2021 with a 1-month history of progressively worsening exertional dyspnea and fatigue.He had previously been able to walk across a golf course without discomfort but now needed a golf cart, and he became breathless during light activities such as getting dressed.He reported no fevers, chills, night sweats, cough, chest discomfort, orthopnea, swelling of the arms or legs, weight gain, or bloody stools.He also had a new onset of headaches on awakening that were worse when he was in the supine position and abated with the use of aspirin, acetaminophen, and caffeine.Subacute dyspnea on exertion can be caused by cardiovascular and pulmonary disease, as well as by neuromuscular disorders, anemia, metabolic disturbances, and physical deconditioning.Characterizing the quality, triggers, and tempo of dyspnea can help to determine its cause.The subacute onset of air hunger is unlikely to represent new obstructive lung disease, but it could be a symptom of a wide variety of cardiovascular diseases including coronary atherosclerosis, arrhythmia, valvulopathy, heart failure, and pericardial effusion, as well as diseases of the alveoli, lung parenchyma, and pulmonary vasculature.New morning headaches in a patient older than 50 years of age that are worse when the patient is in the supine position merit neuroimaging to rule out a space-occupying lesion; however, headache in association with dyspnea might reflect multifocal infection or hypoxia in the context of cardiac or pulmonary disease.
Effectiveness of a Meningococcal Group B Vaccine (4CMenB) in Children
Authors: Jesús Castilla, Manuel García Cenoz, Raquel Abad, Laura Sánchez-Cambronero, Nicola Lorusso, Conchita Izquierdo, Soledad Cañellas Llabrés, Javier Roig, Alberto Malvar, Fernando González Carril, An L.D. Boone, Jaime Pérez Martín, M. Jesús Rodríguez Recio, Antònia Galmés, Arturo Caballero, Amós García Rojas, Felipe Juanas, Mercedes Nieto, Luis J. Viloria Raymundo, Eva Martínez Ochoa, Ana I. Rivas, Daniel Castrillejo, David Moreno Pérez, Ana Martínez, Eva Borràs, Amaya Sánchez Gómez, Eliseo Pastor, Victoria Nartallo, José M. Arteagoitia, Blanca Álvarez-Fernández, Rocío García Pina, Socorro Fernández Arribas, Joana Vanrell, Sara García Hernández, Rita M. Mendoza, Manuel Méndez, M. Mar López-Tercero, Ángela Fernández-Rodríguez, Ángela Blanco, F. Javier Carrillo de Albornoz, José Ruiz Olivares, Rafael Ruiz-Montero, Aurora Limia, José A. Navarro-Alonso, Julio A. Vázquez, Aurelio Barricarte
Journal: New England Journal of Medicine (2023)

In September 2015, the four-component, protein-based meningococcal serogroup B vaccine (4CMenB; Bexsero) became available for private purchase in Spain.We conducted a nationwide matched case-control study to assess the effectiveness of 4CMenB in preventing invasive meningococcal disease in children. The study included all laboratory-confirmed cases of invasive meningococcal disease in children younger than 60 months of age between October 5, 2015, and October 6, 2019, in Spain. Each case patient was matched with four controls according to date of birth and province. 4CMenB vaccination status of the case patients and controls was compared with the use of multivariate conditional logistic regression.We compared 306 case patients (243 [79.4%] with serogroup B disease) with 1224 controls. A total of 35 case patients (11.4%) and 298 controls (24.3%) had received at least one dose of 4CMenB. The effectiveness of complete vaccination with 4CMenB (defined as receipt of at least 2 doses, administered in accordance with the manufacturer's recommendations) was 76% (95% confidence interval [CI], 57 to 87) against invasive meningococcal disease caused by any serogroup, and partial vaccination was 54% (95% CI, 18 to 74) effective. Complete vaccination resulted in an effectiveness of 71% (95% CI, 45 to 85) against meningococcal serogroup B disease. Vaccine effectiveness with at least one dose of 4CMenB was 64% (95% CI, 41 to 78) against serogroup B disease and 82% (95% CI, 21 to 96) against non-serogroup B disease. With the use of the genetic Meningococcal Antigen Typing System, serogroup B strains that were expected to be covered by 4CMenB were detected in 44 case patients, none of whom had been vaccinated.Complete vaccination with 4CMenB was found to be effective in preventing invasive disease by serogroup B and non-serogroup B meningococci in children younger than 5 years of age.
Malaria — Epidemiology, Treatment, and Prevention
Authors: Lindsey Baden, Flaminia Catteruccia, Abdoulaye Diabaté, Cristina Donini, François Nosten, Scott O’Neill, Faith Osier, Aung Pyae Phyo, Nicholas White
Journal: New England Journal of Medicine (2023)

In this documentary video from the New England Journal of Medicine, physicians and scientists from across the world discuss the epidemiology of malaria and outline key strategies for prevention and treatment of the disease. The narrative takes a deep dive into prevention of the disease, including strategies to control mosquito vectors, new vaccines, and monoclonal antibodies. The video anticipates the challenges of eliminating malaria, given the emergence of drug-resistant strains, and looks to promising new therapies on the horizon. For further reading, the following articles, referenced in this video, are available at the Journal's website: A Malaria Vaccine for Africa — An Important Step in a Century-Long Quest , in the March 17, 2022, issue; Safety and Efficacy of a Monoclonal Antibody against Malaria in Mali in the November 17, 2022, issue; and Low-Dose Subcutaneous or Intravenous Monoclonal Antibody to Prevent Malaria, in the November 17, 2022, issue. This video includes footage and photos provided by the Global Fund to Fight AIDS, Tuberculosis, and Malaria; MMV Medicines for Malaria Venture; Caz Tanner; Suphak Nosten for Shoklo Malaria Research Unit; and Saw HTEE K Paung for Shoklo Malaria Research Unit.
Consensus proposal for revised International Working Group response criteria for higher risk myelodysplastic syndromes
Authors: Amer M. Zeidan, Uwe Platzbecker, Jan Philipp Bewersdorf, Maximilian Stahl, Lionel Adès, Uma Borate, David T Bowen, Rena J. Buckstein, Andrew M. Brunner, Hetty E Carraway, Naval G. Daver, Maria Díez-Campelo, Theo M de Witte, Amy E. DeZern, Fabio Efficace, Guillermo Garcia-Manero, Jacqueline S. Garcia, Ulrich Germing, Aristoteles Giagounidis, Elizabeth A Griffiths, Robert P Hasserjian, Eva Hellström-Lindberg, Marcelo C Iastrebner, Rami S. Komrokji, Austin G Kulasekararaj, Luca Malcovati, Yasushi Miyazaki, Olatoyosi Odenike, Valeria Santini, Guillermo F. Sanz, Phillip Scheinberg, Reinhard Stauder, Arjan A Van de Loosdrecht, Andrew H Wei, Mikkael A. Sekeres, Pierre Fenaux
Journal: Blood (2023)
Rngtt governs biliary-derived liver regeneration initiation by transcriptional regulation of mTORC1 and Dnmt1 in zebrafish
Authors: Jianlong Ma, Zhuolin Yang, Zhuofu Huang, Linke Li, Jingliang Huang, Jingying Chen, Rui Ni, Lingfei Luo, Jianbo He
Journal: Hepatology (2023)

In cases of end-stage liver diseases, the proliferation of existing hepatocytes is compromised, a feature of human chronic liver disease, in which most hepatocytes are dysfunctional. So far, liver transplantation represents the only curative therapeutic solution for advanced liver diseases, and the shortage of donor organs leads to high morbidity and mortality worldwide. The promising treatment is to prompt the biliary epithelial cells (BECs) transdifferentiation. However, the critical factors governing the initiation of BEC-derived liver regeneration are largely unknown. The zebrafish has advantages in large-scale genetic screens to identify the critical factors involved in liver regeneration. Here, we combined N-ethyl-N-nitrosourea screen, positional cloning, transgenic lines, antibody staining, and in situ hybridization methods and identified a liver regeneration defect mutant (lrd) using the zebrafish extensive liver injury model. Through positional cloning and genomic sequencing, we mapped the mutation site to rngtt. Loss of rngtt leads to the defects of BEC dedifferentiation, bipotential progenitor cell activation, and cell proliferation in the initiation stage of liver regeneration. The transdifferentiation from BECs to hepatocytes did not occur even at the late stage of liver regeneration. Mechanically, Rngtt transcriptionally regulates the attachment of mRNA cap to mTOR complex 1 (mTORC1) components and dnmt1 to maintain the activation of mTORC1 and DNA methylation in BECs after severe liver injury and prompt BEC to hepatocyte conversion. Furthermore, rptor and dnmt1 mutants displayed the same liver regeneration defects as rngtt mutation. In conclusion, our results suggest Rngtt is a new factor that initiates BEC-derived liver regeneration. Export
The influence of microbial dysbiosis on immunochemotherapy-related efficacy and safety in diffuse large B-cell lymphoma
Authors: Sang Eun Yoon, Woorim Kang, Seunghyun Choi, Yoon Park, Mauricio Chalita, Hyun Kim, Je Hee Lee, Dong-Wook Hyun, Kyung Ju Ryu, Hojun Sung, Jae-Yun Lee, Jin-Woo Bae, Won Seog Kim, Seok-Jin Kim
Journal: Blood (2023)
Omecamtiv Mecarbil in Black Patients With Heart Failure and Reduced Ejection Fraction
Authors: David E. Lanfear, Joyce N. Njoroge, Kirkwood F. Adams, Inder Anand, James C. Fang, Felix Ramires, Karen Sliwa-Hahnle, Aysha Badat, Lesley Burgess, Eiran Z. Gorodeski, Celeste Williams, Rafael Diaz, Gary M. Felker, John J.V. McMurray, Marco Metra, Scott Solomon, Zi Michael Miao, Brian L. Claggett, Stephen B. Heitner, Stuart Kupfer, Fady I. Malik, John R. Teerlink
Journal: JACC Heart Failure (2023)

Omecamtiv mecarbil improves cardiovascular outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Consistency of drug benefit across race is a key public health topic.The purpose of this study was to evaluate the effect of omecamtiv mecarbil among self-identified Black patients.In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) patients with symptomatic HF, elevated natriuretic peptides, and left ventricular ejection fraction (LVEF) ≤35% were randomized to omecamtiv mecarbil or placebo. The primary outcome was a composite of time to first event of HF or cardiovascular death. The authors analyzed treatment effects in Black vs White patients in countries contributing at least 10 Black participants.Black patients accounted for 6.8% (n = 562) of overall enrollment and 29% of U.S. enrollment. Most Black patients enrolled in the United States, South Africa, and Brazil (n = 535, 95%). Compared with White patients enrolled from these countries (n = 1,129), Black patients differed in demographics, comorbid conditions, received higher rates of medical therapy and lower rates of device therapies, and experienced higher overall event rates. The effect of omecamtiv mecarbil was consistent in Black vs White patients, with no difference in the primary endpoint (HR = 0.83 vs 0.88, P-interaction = 0.66), similar improvements in heart rate and N-terminal pro-B-type natriuretic peptide, and no significant safety signals. Among endpoints, the only nominally significant treatment-by-race interaction was the placebo-corrected change in blood pressure from baseline in Black vs White patients (+3.4 vs -0.7 mm Hg, P for interaction = 0.02).GALACTIC-HF enrolled more Black patients than other recent HF trials. Black patients treated with omecamtiv mecarbil had similar benefit and safety compared with White counterparts.
Predictors of Incident Heart Failure Diagnosis Setting
Authors: Rebecca L. Tisdale, Jun Fan, Jamie Calma, Kevin Cyr, Tanya Podchiyska, Randall S. Stafford, David J. Maron, Tina Hernandez-Boussard, Andrew Ambrosy, Paul A. Heidenreich, Alexander T. Sandhu
Journal: JACC Heart Failure (2023)
Patient-Reported Frailty and Functional Status in Heart Failure With Preserved Ejection Fraction
Authors: Padma Kaul, Sarah Rathwell, Carolyn S.P. Lam, Cynthia M. Westerhout, John A. Spertus, Kevin J. Anstrom, Robert O. Blaustein, Justin A. Ezekowitz, Burkert Pieske, Lothar Roessig, Javed Butler, Paul W. Armstrong
Journal: JACC Heart Failure (2023)
Comparison of Investigator-Reported and Centrally Adjudicated Heart Failure Outcomes in the EMPEROR-Reduced Trial
Authors: Peter Carson, John R. Teerlink, Michel Komajda, Inder Anand, Stefan D. Anker, Javed Butler, Wolfram Doehner, João Pedro Ferreira, Gerasimos Filippatos, Markus Haass, Alan Miller, Steen Pehrson, Stuart J. Pocock, Sven Schnaidt, Janet M. Schnee, Faiez Zannad, Milton Packer
Journal: JACC Heart Failure (2023)

There is limited published information on outcome adjudication in heart failure (HF).The authors sought to compare investigator reports (IRs) to a Clinical Events Committee (CEC) and the impact of SCTI (Standardized Clinical Trial Initiative) criteria.In the EMPEROR-Reduced trial, the authors compared IRs to the CEC for concordance; treatment effect on primary composite outcome events; and the components first event hospitalization primarily for HF or cardiovascular mortality (CVM), prognosis after hospitalization for heart failure (HHF), total HHFs, and trial duration with and without SCTI criteria.The CEC confirmed 76.3% of IR events for the primary outcome (CVM: 89.1%; HHF: 73.7%). The HR for treatment effect did not differ between adjudication methods for the primary outcome (IR: 0.75 [95% CI: 0.66-0.85]; CEC: 0.75 [95% CI: 0.65-0.86]), its components, or total HHFs. The prognosis after first HHF for all-cause mortality and CVM also did not differ between IR or CEC. Interestingly, IR primary HHF with different CEC primary cause had the highest subsequent fatal event rate. Full SCTI criteria were present in 90% of CEC HHFs-with a similar treatment effect to non-SCTI. The IR primary event reached the protocol target number (841) 3 months earlier than CEC (4 months with full SCTI criteria).Investigator adjudication is an alternative to a CEC with similar accuracy and faster event accumulation. The use of granular (SCTI) criteria did not improve trial performance. Finally, our data suggest that consideration be given to broadening the HHF definition to include "for or with" worsening disease. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977).
Dapagliflozin in Black and White Patients With Heart Failure Across the Ejection Fraction Spectrum
Authors: Jawad H. Butt, Kieran F. Docherty, Brian L. Claggett, Akshay S. Desai, James C. Fang, Magnus Petersson, Anna Maria Langkilde, Rudolf A. de Boer, Jose Walter Cabrera Honorio, Adrian F. Hernandez, Silvio E. Inzucchi, Mikhail N. Kosiborod, Lars Køber, Carolyn S.P. Lam, Felipe A. Martinez, Piotr Ponikowski, Marc S. Sabatine, Orly Vardeny, Eileen O'Meara, Jose F.K. Saraiva, Sanjiv J. Shah, Muthiah Vaduganathan, Pardeep S. Jhund, Scott D. Solomon, John J.V. McMurray
Journal: JACC Heart Failure (2023)
Association of Social Isolation and Loneliness With Incident Heart Failure in a Population-Based Cohort Study
Authors: Yannis Yan Liang, Yilin Chen, Hongliang Feng, Xiangxin Liu, Qi-Yong H. Ai, Huachen Xue, Xinyue Shu, Foqian Weng, Zhixuan He, Jiacheng Ma, Huan Ma, Sizhi Ai, Qingshan Geng, Jihui Zhang
Journal: JACC Heart Failure (2023)
Reclassification of Pre-Heart Failure Stages Using Cardiac Biomarkers
Authors: Xiaoming Jia, Mahmoud Al Rifai, Chiadi E. Ndumele, Salim S. Virani, James A. de Lemos, Emmanuel Lee, Amil M. Shah, Justin B. Echouffo-Tcheugui, Biykem Bozkurt, Ron Hoogeveen, Elizabeth Selvin, Christie M. Ballantyne, Vijay Nambi
Journal: JACC Heart Failure (2023)
Additive efficacy of a bispecific anti–TNF/IL-6 nanobody compound in translational models of rheumatoid arthritis
Authors: Nadine Biesemann, Daniel Margerie, Christian Asbrand, Markus Rehberg, Virginia Savova, Inoncent Agueusop, Daniel Klemmer, Danping Ding-Pfennigdorff, Uwe Schwahn, Markus Dudek, Karen Heyninck, Evelyn De Tavernier, Sigrid Cornelis, Markus Kohlmann, Frank O. Nestle, Matthias Herrmann
Journal: Science Translational Medicine (2023)

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases affecting primarily the joints. Despite successful therapies including antibodies against tumor necrosis factor (TNF) and interleukin-6 (IL-6) receptor, only 20 to 30% of patients experience remission. We studied whether inhibiting both TNF and IL-6 would result in improved efficacy. Using backtranslation from single-cell RNA sequencing (scRNA-seq) data from individuals with RA, we hypothesized that TNF and IL-6 act synergistically on fibroblast-like synoviocytes (FLS) and T cells. Coculture of FLS from individuals with RA and T cells supported this hypothesis, revealing effects on both disease-driving pathways and biomarkers. Combining anti-TNF and anti–IL-6 antibodies in collagen-induced arthritis (CIA) mouse models resulted in sustained long-term remission, improved histology, and effects on bone remodeling pathways. These promising data initiated the development of an anti–TNF/IL-6 bispecific nanobody compound 1, with similar potencies against TNF and IL-6. We observed additive efficacy of compound 1 in a FLS/T cell coculture affecting arthritis and T helper 17 (T H 17) pathways. This nanobody compound transcript signature inversely overlapped with described RA endotypes, indicating a potential efficacy in a broader patient population. In summary, we showed superiority of a bispecific anti–TNF/IL-6 nanobody compound or combination treatment over monospecific treatments in both in vitro and in vivo models. We anticipate improved efficacy in upcoming clinical studies.